Stille couplings catalytic in tin: Beyond proof-of-principle

Full text of DOI:10.1021/ja993446s

384
J. Am. Chem. Soc. 2000, 122, 384-385
Communications to the Editor
Stille Couplings Catalytic in Tin: Beyond
Proof-of-Principle
Scheme 1
Robert E. Maleczka, Jr.,* William P. Gallagher, and
Ina Terstiege
Department of Chemistry, Michigan State UniVersity
East Lansing, Michigan 48824
ReceiVed September 23, 1999
1
Stille cross-couplings often involve the palladium-catalyzed
union of vinyl or aryl halides with vinylstannanes to form 1,3-
dienes. Stille reactions are quite tolerant to a large array of
functionality, typically proceed with a conservation of olefin
geometry, and are most often regiospecific with regards to the
newly formed C-C σ-bond. As such, Stille reactions have proven
Scheme 2
2
useful in natural product synthesis, the construction of new
3
4
5
materials, heterocycle preparation, carbohydrate chemistry, and
6
support of bioorganic research. Furthermore, Stille couplings are
quite compatible with various new technologies. They behave well
2
a,7
in a combinatorial setting,
are rapidly accelerated under
8
The invention of such a catalytic method poses several
challenges. Perhaps most fundamental among these is that while
many important advances in the development of catalytic versions
of tin-mediated reactions have been realized,1 most prior efforts
microwave irradiation, have proven amenable to reaction in the
fluorous phase,8 and offer great potential in the very nonpolar
b,9
10
environment of supercritical carbon dioxide. Despite such
synthetic utility, a historic drawback of the Stille reaction has
been its reliance on stoichiometric quantities of toxic, costly, and
occasionally unstable organostannanes.1 Therefore, we believe
a Stille reaction, which is catalytic in tin, would be of considerable
benefit.13
1,14
3 2
have focused on tin reagents such as Bu SnH, Bu SnO, (BuCH-
1,12
(Et)CO SnBu, etc. Little attention has been given to the
2 3
)
invention of catalytic variants for chemical transformations, where
the organotin species is a reactant covalently bonded to the organic
molecular material of interest. In short, rendering the Stille
reaction catalytic in tin would require an initial molecule of
organotin hydride to participate in a chemoselective sequence of
in situ vinyltin generation, cross-coupling, and then a final
transformation of the organotin halide byproduct back to tin
hydride.
(
1) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508-523. (b)
Stille, J. K.; Groh, B. L. J. Am. Chem. Soc. 1987, 109, 813-817. (c) Farina,
V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1997, 50, 1-652.
(
2) For examples see: (a) Nicolaou, K. C.; Winssinger, N.; Pastor, J.;
Murphy, F. Angew. Chem., Int. Ed. Engl. 1998, 37, 2534-2537. (b) Alcaraz,
L.; Macdonald, G.; Ragot, J.; Lewis, N. J.; Taylor, R. J. K. Tetrahedron 1999,
5
5, 3707-3716. (c) Duncton, M. A. J.; Pattenden, G. J. Chem. Soc., Perkin
Trans. 1 1999, 1235-1246.
Our initial efforts on the development of such a reaction
(
3) For examples see: (a) Yao, Y. X.; Tour, J. M. Macromolecules 1999,
1
4a,15
3
7
2, 2455-2461. (b) Hucke, A.; Cava, M. P. J. Org. Chem. 1998, 63, 7413-
sequence were reported last year.
In the first of these early
417.
(
15
studies, we established a one-pot palladium-mediated hydrostan-
nylation/ Stille cross-coupling protocol. Furthermore, by running
4) For an example see: Beccalli, E. M.; Clerici, F.; Gelmi, M. L.
Tetrahedron 1999, 55, 781-786.
5) For an example see: Kuribayashi, T.; Gohya, S.; Mizuno, Y.; Satoh,
S. J. Carbohyd. Chem. 1999, 18, 383-392.
6) For examples see: (a) Nicolaou, K. C.; King, N. P.; Finlay, M. R. V.;
(
2 3
the reaction sequence in the presence of aqueous Na CO and
polymethylhydrosiloxane (PMHS), in situ conversion of the
tributyltin halide Stille byproduct into a tin oxide species, followed
(
He, Y.; Roschangar, F.; Vourloumis, D.; Vallberg, H.; Sarabia, F.; Ninkovic,
S.; Hepworth, D. Bioorg. Med. Chem. 1999, 7, 665-697. (b) Thibonnet, T.
J.; Abarbri, M.; Duchene, A.; Parrain, J. L. Synlett 1999, 141-143.
16
17
by PMHS reduction of the newly formed Sn-O bond,
regenerated Bu SnH and established our catalytic cycle (Scheme
1). In these first examples of tin-catalyzed Stille cross-couplings,
SnCl afforded 1,3-dienes in
3
(
7) (a) Lorsbach, B. A.; Kurth, M. J. Chem. ReV. 1999, 99, 1549-1581.
(
b) Booth, S.; Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. C.
Tetrahedron 1998, 54, 15385-15443 and references therein.
8) (a) Larhed, M.; Hoshino, M.; Hadida, S.; Curran, D. P.; Hallberg, A.
the employment of 4-10 mol % Bu
3
(
approximately 22-26% yield, representing a very modest 2-5
J. Org. Chem. 1997, 62, 5583-5587. (b) Olofsson, K.; Kim, S.-Y.; Larhed,
M.; Curran, D. P.; Hallberg, A. J. Org. Chem. 1999, 64, 4539-4541.
tin turnovers (Scheme 2).
(
9) (a) Hoshino, M.; Degenkolb, P.; Curran, D. P. J. Org. Chem. 1997, 62,
In part, these less than ideal results can be traced to the
sluggishness (48-72 h) of the cross-coupling portion of our
sequence. This allows the tin ample time to react in nonproductive
8
2
341-8349. (b) Curran, D. P.; Hadida, S. J. Am. Chem. Soc. 1996, 118, 2531-
532.
(
(
10) Jessop, P. G.; Ikariya, T.; Noyori, R. Chem. ReV. 1999, 99, 475-493.
11) (a) Chemistry of Tin; Smith, P. J., Ed.; Blackie Academic &
Professional: New York, 1998. (b) Davies, A. G. In Organotin Chemistry;
VCH: New York, 1997.
(
(14) (a) Terstiege, I.; Maleczka, R. E., Jr. J. Org. Chem. 1999, 64, 342-
343. (b) Martinelli, M. J.; Nayyar, N. K.; Moher, E. D.; Dhokte, U. P.; Pawlak,
J. M.; Vaidyanathan, R. Org. Lett. 1999, 1, 447-450. (c) Spino, C.; Barriault,
N. J. Org. Chem. 1999, 64, 5292-5298. (d) Lopez, R. M.; Fu, G. C.
Tetrahedron 1997, 53, 16349-16354. (e) Hays, D. S.; Fu, G. C. Tetrahedron
1999, 55, 8815-8832 and references therein.
12) (a) Hitchcock, S. A.; Mayhugh, D. R.; Gregory, G. S. Tetrahedron
Lett. 1995, 36, 9085-9088. (b) Zhang, H. X.; Guib e´ , F.; Balavoine, G. J.
Org. Chem. 1990, 55, 1857-1867.
(
13) Problems associated with the employment of tin in the Stille reaction
have, in part, fueled the development of “tin free” cross-coupling protocols,
most prominently the Suzuki coupling. Though a powerful method, the Suzuki
coupling has not supplanted the Stille reaction as a synthetic tool. Evidence
(15) Maleczka, R. E., Jr.; Terstiege, I. J. Org. Chem. 1998, 63, 9622-
9623.
1
a
of this can be seen in a 1997-1999 ISI citation search, of the primary Stille
and Suzuki (Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483)
reviews. Such a search reveals a comparable 420 and 350 citations of the
Stille and Suzuki reviews, respectively.
(16) Hayashi, K.; Iyoda, J.; Shiihara, I. J. Organomet. Chem. 1967, 10,
81-94.
(17) We assume the “Sn-O” species to be an organotin carbonate.
However, this has yet to be firmly established.
1
0.1021/ja993446s CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/31/1999

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 2, 2000 385
Scheme 3
Scheme 4
yield, representing an average of ∼15 tin turnovers. Furthermore,
since one cycle requires the tin to undergo four transformations,
each molecule of organostannane is experiencing a minimum of
60 reactions over the course of the hydrostannylation/Stille
sequence. Significantly, all Stille products were formed in similar
or superior yields to those realized under “classic” two-pot,
stoichiometric conditions.
Little improvement was observed in the efficiency of these
3
reactions when higher loads of Me SnCl were employed. How-
ever, dropping below 6 mol % tin resulted in fairly substantial
reductions in yield (Scheme 4). For example, at 1 mol % Me
3
-
SnCl, the 1,3-diene was formed in only 18% yield.
Work to improve the turnover numbers of our protocol will
continue, as will our efforts to more fully address the regiochemi-
cal impact of carrying out the reaction sequence with sterically
less demanding alkynes.21 We also seek to balance the increased
safety concerns associated with trimethylstannanes.1 Nonethe-
less, our method for performing one-pot hydrostannylation/Stille
couplings with catalytic amounts of tin has advanced beyond the
proof-of-principle stage, with us now able to form diverse arrays
of Stille products in excellent yields, while at the same time
reducing the traditional tin requirement by 94%.
1,22
Acknowledgment. Generous support was provided by the NIH (HL-
8114) and MSU from an Intramural Research Grant and start-up funds
for R.E.M. We also thank Mr. Damon Clark and Ms. Susan Whitehead
for running important control experiments.
ways, i.e., formation of hexabutylditin.18 Since it is generally
believed that transmetalation is the rate-determining step of the
Stille reaction, we rationalized that switching from tributyltins
5
1
to the less sterically demanding trimethyltins should facilitate the
overall reaction sequence.
Supporting Information Available: Spectroscopic data for all new
compounds pictured, as well as detailed experimental procedures (PDF).
This material is available free of charge via the Internet at http:/pubs.acs.org.
19
As illustrated in Scheme 3, syringe pump addition of 1.5 equiv
of various Stille electrophiles to a 37 °C ethereal mixture of
alkyne, aqueous Na
2
CO
and 0.06 equiv of Me
h afforded the corresponding cross-coupled products in 75-91%
3
, PMHS, Pd
2
dba
3
, trifurylphosphine,
JA993446S
20
PdCl
2
3
(PPh )
2
,
3
SnCl over a period of 15
(
2
20) Though the reason remains unclear, the mixed Pd system of 1 mol %
dba , 4 mol % (2-furyl) P, and 1 mol % PdCl (PPh in Et O gave the
best yields.
Pd
3
3
2
)
3 2
2
(
18) Attempts to accelerate the reaction through the use of polar solvents
DMF or NMP) or highly active catalysts such as (MeCN) PdCl resulted in
overall diminished yields, as Pd-catalyzed conversion of Bu SnH into
(21) We limited this study to R-trisubstituted alkynes containing a lone
pair on one of the propargylic substituents as bulky alkynes give (E)-
vinylstannanes upon Pd-catalyzed hydrostannylation. (See: (a) Blaskovich,
M. A.; Kahn, M. J. Org. Chem. 1998, 63, 1119-1125. (b) Betzer, J.-F.;
Delaloge, F.; Muller, B.; Pancrazi, A.; Prunet, J. J. Org. Chem. 1997, 62,
7768-7780.) Detailed studies of our protocol under less regiocontrolled
circumstances are underway. We will report the results of these investigations
as they develop.
(22) (a) Scott, W. J.; Moretto, A. F. In Encyclopedia of Reagents for
Organic Synthesis; Paquette, L., Ed.; Wiley: New York, 1995; Vol 7, pp
5327-5328. (b) Dyer, R. S.; Walsh, T. J.; Wonderlin, W. F.; Bercegeay, M.
NeurobehaV. Toxicol. Teratol. 1982, 4, 127-133.
(
2
2
3
hexabutylditin (Mitchell, T. N.; Amamria, A.; Killing, H.; Rutschow, D. J.
Organomet. Chem. 1986, 304, 257-265) predominated the reaction. Further-
more, the addition of copper salts provided little or no improvement (see: (a)
Allred, G. D.; Liebeskind, L. S. J. Am. Chem. Soc. 1996, 118, 2748-2749.
(
b) Han, X. J.; Stoltz, B. M.; Corey, E. J. J. Am. Chem. Soc. 1999, 121, 7600-
7
605).
19) Addition of the electrophiles, particularly the iodides, in a single portion
resulted in intrusive levels of hydrodehalogenation, presumably via Pd(0)-
catalyzed reduction by PMHS/Na CO
(
2
3
.